A Randomized, Multicenter, Double-Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of IgPro10 (Intravenous Immunoglobulin, Privigen®) for the Treatment of Adults With Systemic Sclerosis

CSL Behring77 sites in 8 countriesDecember 20, 2019

ConditionsDiffuse Cutaneous Systemic Sclerosis

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Diffuse Cutaneous Systemic Sclerosis
Sponsor: CSL Behring
Locations: 77
Primary Endpoint: Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo
Status: Withdrawn
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This randomized, multicenter, double-blind (DB), placebo controlled, phase 2 study will evaluate the efficacy and safety of IgPro10. The DB Treatment Period will be followed by a 24-week Open-label (OL) Treatment Period.

Eligible subjects will be randomized at Baseline in a 2:1 ratio of treatment IgPro10 or placebo in the DB Treatment Period. All subjects who enter OL Treatment Period will receive IgPro10.

Registry

clinicaltrials.gov

Start Date

December 20, 2019

End Date

September 16, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

CSL Behring

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥18 years (male or female) at time of providing written informed consent
•Documented diagnosis of SSc according to ACR / EULAR criteria 2013
•mRSS ≥ 15 and ≤ 45
•Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation
•Subjects within first 18 months of disease duration from first non-Raynaud's phenomenon manifestation.

Exclusion Criteria

•Primary rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, and dermatomyositis, as determined by the investigator Note: Subjects with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy or myositis at Screening are not excluded
•Positive anti-centromere autoantibodies at Screening
•Evidence of severe chronic kidney disease with estimated glomerular filtration rate \< 45 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) or receiving dialysis. Additionally, subjects with current confirmed diagnosis of diabetes mellitus and requiring medication, with eGFR \< 90 mL/min/1.73m2 will be excluded from the study.
•History of documented thrombotic episode eg, PE, DVT, myocardial infarction, thromboembolic stroke at any time Note: past superficial thrombophlebitis more than two years from Screening is not exclusionary
•Documented thrombophilic abnormalities including blood hyperviscosity, protein S or protein C deficiency, anti-thrombin-3 deficiency, plasminogen deficiency, antiphospholipid syndrome, Factor V Leiden mutation, dysfibrinogenemia, or prothrombin G20210A mutation
•Greater than 3 specified current risk factors for TEEs (documented and currents conditions): atrial fibrillation, coronary disease, diabetes mellitus, dyslipidemia, hypertension, obesity (Body Mass Index ≥ 30 kg/m2), recent significant trauma, and immobility (wheelchair-bound or bedridden)
•Ongoing active serious infection at Screening (including, but not limited to, pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess)
•Malignancy in the past 2 years, except for non-melanoma skin cancer, cervical carcinoma in situ, or other in situ cancer if it has been excised and treated within in the past year
•Known hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration \> 0.2 g/L)
•Known IgA deficiency or serum IgA level \< 5% lower limit of normal

Outcomes

Primary Outcomes

Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo

Time Frame: Over 48 weeks

Secondary Outcomes

Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events(Over 48 weeks)
Proportion of responders (ACR CRISS > 0.6)(Over 72 weeks)
Mean change from Baseline in Modified Rodnan Skin Score (mRSS)(Baseline and over48 weeks)
Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)(Baseline and over 72 weeks)
Mean change from Baseline in Forced Vital Capacity (FVC)% predicted(Baseline and over 72 weeks)
Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted(Baseline and over 72 weeks)
Mean change from Baseline in Physician Global Assessment (MDGA)(Baseline and over 72 weeks)
Mean change from Baseline in Patient Global Assessment (PGA)(Baseline and over 48 weeks)
Mean change from Baseline in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) total score and subscale(Baseline and over 48 weeks)
Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo(Baseline and up to 48 weeks)
Proportion of responders in mRSS(Up to 48 weeks)
Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo(Over 48 weeks)
Proportion of subjects with events at Week 48 in IgPro10 vs Placebo(Over 48 weeks)
Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo(Baseline and over 48 weeks)
Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo(Baseline and over 48 weeks)
Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo(Baseline and over 48 weeks)
Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)(Over 72 weeks)
Percentage of subjects with AEs, TEAEs, SAEs, AESIs(Over 72 weeks)
Concentration of serum trough IgG levels at Baseline and prior to first infusion(Baseline and up to 72 weeks)
Mean change from Baseline in Modified Rodnan skin score (mRSS)(Baseline and over 72 weeks)
Mean change from Baseline in Patient global assessment (PGA)(Baseline and over 72 weeks)